Anti-infective central venous catheter with diffusion barrier layer

ABSTRACT

A catheter extending from a distal end which, when in an operative position is inserted within a body of a patient, to a proximal end, the catheter comprising a charge holding cavity to which a therapeutic compound is to be supplied and a wall including inner and outer portions, an inner surface of the inner portion surrounding the charge holding cavity with an outer portion surrounding at least a portion of an outer surface of the inner portion, wherein the inner portion is formed so that a first diffusion rate of the therapeutic compound therethrough is different from a second diffusion rate through the outer portion.

BACKGROUND INFORMATION

[0001] Many medical procedures require repeated and prolonged access toa patient's vascular system. For example, during treatment of diabeticpatients, blood is removed for filtering and purification externally tothe body, to make up for the inability of the patient's kidneys to carryout that function naturally. In other procedures, access to thepatient's vascular system is necessary to administer antibiotics, drugs,nutrition or chemotherapy agents on a long term basis. Typically accessis obtained through a vein or artery, using a catheter secured to thepatient and a needle of the catheter penetrating the blood vessel.

[0002] Some of these procedures are repeated several times a week and itis impractical and dangerous to insert and remove the catheter for eachprocedure. The catheter thus is implanted semi permanently with a distalend remaining within the patient, in contact with the vascular system,and a proximal end remaining external to the patient's body. Theproximal end is sealed after the medical session is completed, toprevent blood loss and infections. The distal end of the catheter thusremains in the patient's body, often for extended periods of time. Insome cases, the catheter may be sutured in place and remain within thepatient for several years.

[0003] A clinical drawback to leaving these devices in the patient forextended periods is that bacteria tends to attach to the surfaces of thecatheter, multiply, and produce a biofilm layer that can result insepsis. These infections may lead to severe complications that often aredebilitating and may be life-threatening. Anti-infective agentsincluding, for example, antibiotic and other antimicrobial coatings,have been used on the catheters to combat these infections. For example,chlorhexidine-silver sulfadiazine and rifampin-myinocycline coatings,among others, have been applied to the polymeric surfaces of catheters.This solution however has not proved satisfactory, as the agents in thecoatings are often released in a short time interval after implantationof the device, soon leaving the catheter open to infection.

SUMMARY OF THE INVENTION

[0004] The present invention is directed to a catheter extending from adistal end which, when in an operative position, is inserted within abody of a patient to a proximal end, the catheter comprising a chargeholding cavity to which a therapeutic compound is to be supplied and awall including inner and outer portions, an inner surface of the innerportion surrounding the charge holding cavity with an outer portionsurrounding at least a portion of an outer surface of the inner portion,wherein the inner portion is formed so that a first diffusion rate ofthe therapeutic compound therethrough is different from a seconddiffusion rate through the outer portion.

BRIEF DESCRIPTION OF DRAWINGS

[0005]FIG. 1 is a schematic diagram of a vascular access catheter;

[0006]FIG. 2 is a schematic drawing of a vascular access catheterinserted in a patient's vein;

[0007]FIG. 3 is a diagram of a catheter cross section according to anembodiment of the present invention;

[0008]FIG. 4 is a diagram of a catheter cross section with dual materialwalls according to another embodiment of the present invention;

[0009]FIG. 5 is a diagram of a catheter cross section with an outersheath according to a third embodiment of the present invention; and

[0010]FIG. 6 is a diagram of a catheter cross section with a differentsheath according to a fourth embodiment of the present invention.

DETAILED DESCRIPTION

[0011] The treatment of many medical conditions requires repeated accessto a patient's venous system for therapeutic sessions, for example, tocarry out transfusions, administer antibiotics, drugs, nutrition orchemotherapy agents to the blood stream, or to purify a patient's blood.Kidney dialysis is one of such treatments which requires chronic accessto patients' blood streams in order to treat chronic renal failure. Inthe case of ailments for which no cure has yet been found, thesetherapeutic sessions may need to be repeated periodically for the lifeof the patient. In many cases the sessions are required several timesper week with each session lasting several hours. Cumulative damage tothe skin and vascular walls caused by repeated punctures makes itimpractical to introduce a new catheter into the patient's venous systemat every session. Accordingly, as described above a semi-permanentlyimplanted catheter is often used, which is maintained in place in thepatient for an extended period of time. The semi-permanently implantedcatheter may then be used whenever access to the venous system isrequired.

[0012] These implantable, semi-permanent vascular access catheters areinserted into and remain partially within the patient for extendedperiods. Examples of such implantable catheters include the chronicdialysis catheters and implantable vascular access systems manufacturedby Boston Scientific Corp. under the trade name Vaxcel™. These devicestypically are inserted through the patient's skin so that a distal endremains under the skin, within the patient's body while a proximal endextends outside the body for connection to an external line. Thesesemi-permanent catheters may be sutured to the patient's skin tomaintain them in place while the patient goes about his or her normaloccupations.

[0013]FIGS. 1 and 2 show an exemplary implantable catheter such as theVaxcel™ Chronic Dialysis Catheter used for kidney dialysis. The catheter10 has a distal end 12 that is insertable under the skin and into thepatient's vein, and which remains within the patient's body for the lifeof the catheter 10. For example, the catheter 10 may remain implanted inthe patient for up to two years or more. As shown more clearly in FIG.2, the distal end 12 is inserted into a vein 8, for example the venacava. During dialysis, blood from the patient is removed through thecatheter 10, and is purified by a dialysis machine (not shown) which isconnected to hubs 18 and 20 of catheter 10 by a dialysis line. Thecatheter 10 in this example includes a first lumen 22 which is used toremove blood from the blood vessel 8 and supply it to the dialysismachine and a second lumen 24 which receives treated blood from thedialysis machine and reintroduces it into the blood vessel 8. The lumen22 terminates at the distal end 12 in an inflow tip 14 while the lumen24 terminates at the distal end 12 in an outflow tip 16. The inflow andoutflow tips 14, 16, respectively, may be staggered (i.e., separatedfrom one another along the length of the distal end 12) to improve aflow of blood through the catheter 10. The first lumen 22 is connectedto an inflow hub 18 while the second lumen 24 is connected to an outflowhub 20. The inflow and outflow hubs 18, 20, respectively are connectedto a proximal part of the catheter 10 which, when the distal end 12 isin position within the blood vessel 8, remains outside the body forconnection to a dialysis line leading to the dialysis machine. That is,the inflow hub 18 may be coupled to a first lumen of a dialysis line forsupplying blood to the dialysis machine while the outflow hub 20 iscoupled to a second lumen of the dialysis line for receiving treatedblood from the dialysis machine and returning it to the blood vessel 8.

[0014] When implanted in the patient's body, infective growth may occurat any point along the portion of the catheter 10 which is within thepatient's body. As indicated above, various coatings containinganti-infective agents have been placed on the surfaces of catheter 10 toprevent the growth of infective agents. In addition, anti-infectiveagents have been supplied in the form of, for example, cuffs includingthe anti-infective agents or a liquid supplied to a lumen of thecatheter which allows anti-infective agents to leach through thecatheter surface to prevent infective growth on or adjacent to the outersurface thereof. However, these methods have often resulted in a toorapid release of the agents which, after a relatively short time, leavesthe catheter 10 exposed to infective growth once again.

[0015] The catheter 10 according to the invention is capable ofdelivering anti-infective agents both intra-luminally andextra-luminally to prevent attachment of bacteria or other infectiveagents to both the inner and outer surfaces of the catheter 10.According to embodiments of the invention, anti-infective agents aredelivered to either or both of the first and second lumens 22, 24,respectively, of the catheter 10, for example, after completion of atherapeutic session such as a dialysis session or chemotherapy session.From the lumen to which the agent is supplied, the compounds can enterthe polymeric wall of the catheter 10 and eventually reach an outersurface thereof where they may impede bacterial or other infectivegrowth. The anti-infective agent may be provided within the lumen eitherin the form of a rod impregnated with the agent, as a liquid solution,or in any other manner as would be understood by those of skill in theart. For example, iodine impregnated rods may be inserted into thelumens 22, 24 or a two part solution of an iodine generating formulationmay be placed in the lumens 22, 24 after the therapeutic procedure hasbeen completed. As discussed above, after the therapeutic treatment hasbeen completed, the proximal ends of the lumens 22, 24 are capped off toprevent infective agents from being introduced into the body via thelumens 22, 24. Thus, once the anti-infective agents have been introducedinto the lumens 22, 24, the capping of the proximal ends of the lumenswill maintain the liquid within the lumens 22, 24 and this liquid willnot enter the blood stream. Then, to access the catheter 10 forsubsequent treatments, treatment personnel need only remove the cap toaccess the lumens 22, 24.

[0016] This system of providing an internally stored quantity ofanti-infective agents within the catheter 10 may be further supplementedby controlling a rate at which the agents pass through the wall of thecatheter 10 to the outer surface thereof. This reduces the need foradditional visits to health care providers to recharge the supply ofanti-infective agents and the costs and inconvenience associated withsuch additional visits. The diffusion rate of the anti-infective agentsis preferably selected so that the anti-infective action continuesthroughout the entire time interval between scheduled therapeuticsessions and may include a tolerance for occasions when a scheduledvisit is delayed or missed.

[0017]FIG. 3 shows an exemplary cross sectional diagram of a catheterwith an anti-infective delivery system according to an embodiment of thepresent invention. In the exemplary embodiment, a dialysis catheter 10is used as a venous catheter that is semi-permanently implanted in apatient. The catheter 10 is formed of a catheter body 40 which includesan outer wall 102 forming an enclosure around a lumen 100. As will beapparent to those skilled in the art, the catheter 10 may include anynumber of additional lumens, and is preferably formed of a flexiblematerial which allows the catheter body 40 to bend, twist, and bedeformed to a certain extent. In its simplest form, the catheter 10 is ahollow tube which includes a single lumen 100 used during therapeuticsessions to carry fluids to and from the patient's vascular system.

[0018] In the embodiment described below, one end of the catheter 10enters a patient's vein, and the other end is connected to a device usedto receive, supply and/or process medical fluids, such as blood as wouldbe understood by those skilled in the art. The outer wall 102 of thecatheter 10 forms a shell-like enclosure around the lumen 100 and has aninner surface 42 which defines the lumen 100 and will be in contact withmaterials 110 placed within the lumen 100. An outer surface 40 of theouter wall 102 is exposed to environment surrounding the catheter 10.For example, the surface 40 may be in contact with the contents of abody lumen into which the catheter 10 has been inserted. In theexemplary case where the catheter 10 is a dialysis catheter implanted ina patient, a proximal portion of the outer surface 40 would be incontact with the tissue through which the catheter 10 was inserted,while a distal portion of the outer surface 40 of the catheter 10 willbe in contact with the blood and/or wall of one or more blood vessels.The lumen 100 may be used to transfer blood between the patient and adialysis machine during treatment, and between treatments may be filledwith an anti-infective or therapeutic compound 110 and sealed at aproximal end thereof. Those skilled in the art will understand that, inaddition to anti-infective agents, the therapeutic compound may be anyagent which it is desired to apply to an outer surface of the catheter10 and, consequently, to be supplied to the surrounding environment at acontrolled rate (e.g., anti-thrombotic, medicinal, nutritional or othersubstances).

[0019] In one embodiment, the therapeutic compound 110 may be ananti-infective agent such as a two part solution of an iodine generatingsolution. In a different embodiment, a rod 108 impregnated with ananti-infective agent such as iodine may be inserted in the lumen 100. Inthis manner, the anti-infective agent can diffuse from the rod 108 overtime, between sessions. When it is necessary to carry out anothertherapeutic session, material is removed from the lumen 100 byaspiration or by other means so that the catheter 10 can be used for itsprincipal function.

[0020] According to exemplary embodiments of the present invention, arate of diffusion of the anti-infective agent from within the catheter10 to the outer surface thereof is controlled to a first pre-selectedrate. In addition, the rate at which the anti-infective agent isabsorbed from the lumen 100 into an inner wall of the catheter 10 mayalso be selected to a second preselected rate so that, for example, theanti-infective agent is quickly absorbed into the catheter 10. Inparticular, the first rate may be selected so that only a necessaryamount of anti-infective agent or other therapeutic compound reaches theouter surface of the catheter 10 at any given time, and so that thecharge of therapeutic compound within the lumen(s) 40 of the catheter 10lasts for a predetermined time interval. In one embodiment, a diffusionbarrier layer is formed at an outer portion 104 of the outer wall 102 ofthe catheter, to reduce the diffusion rate therefrom. With reference toFIG. 3, the outer wall 102 of the catheter 10 is designed to allowdiffusion of the therapeutic compound 110 therefrom at a controlledrate. For example, the outer wall 102 may include an inner portion 106that has properties different than those of the outer portion 104. Inthis embodiment, the durometer hardness of the inner portion 106 isselected to be different than that of the outer portion 104 durometerhardness of a material is one factor which determines the rate at whichiodine is absorbed thereinto. Other factors which may effect this rateare, for example, the addition of additives of different materials tothe resin as described below and the treatment of the surface of thematerial by roughening it or creating openings therein. However, allother factors being equal, an element formed with a higher durometerhardness will generally absorb iodine less quickly than a similarelement of a lower durometer hardness. Thus by using a resin with ahigher hardness to form the outer portion 104, the amount of iodinepassing through the outer surface 40 in a given time is less than itwould have been if the outer portion 104 were made of the same lowerhardness material of which the inner portion 106 is formed. This alsoallows the iodine to be more rapidly absorbed into the inner portion106. This allows for treatments wherein a first injection of iodine ismade into the lumen 100 which iodine is quickly absorbed into the innerportion 106. Then, after a brief waiting period during which the iodineis absorbed into the inner portion 106, the remainder of thesubstantially material in the lumen 100 may be removed and furtherdesired therapeutic agents may then be supplied to the lumen 100.

[0021] In the embodiment shown in FIG. 3, the lower durometer innerportion 106 and the higher durometer outer portion 104 may preferablyformed through co-extrusion of two (2) layers of different materials atthe same time. This method gives rise to a uniform outer wall 102, whichprovides the desired differential between the rate of absorption throughthe inner surface 42 into the inner portion 106 and the rate ofdiffusion from the outer portion 104 through the outer surface 40.

[0022] Alternatively, different diffusion rates of therapeutic compoundsthrough the inner and outer portions 106, 104 may be achieved byreplacing or supplementing the polyurethane in the resin forming wall102 with other compounds having different absorption properties. Forexample as would be understood by those skilled in the art, bariumsulfate, titanium oxide or bismuth sub-carbonate may be added to polymerresins (e.g., polyurethane) to alter the diffusion rates of variouscompounds therethrough. The inclusion of these materials into thepolymers reduces the inter-molecular spaces through which the diffusiontakes place, thereby providing a greater barrier to the diffusion ofiodine and other compounds therethrough. Thus, any of these materials,or a combination thereof, may be added to the material of the outerportion 106 to reduce the rate at which an anti-infective agent suppliedto the lumen 40 reaches the outer surface 40 while, forming the innerportion 106 without the addition of such materials allows anti-infectiveagents to be absorbed thereinto from the lumen 40 at an increased rate.In addition, as would be understood by those of skill in the art, byselecting resins of varying molecular weights, different rates ofabsorption thereinto may also be obtained.

[0023] As described above, forming the outer wall 102 in a co-extrusionprocess may simplify the construction of the catheter 10 while allowingthe properties of the outer wall 102 of the catheter 10 to be tailoredto desired diffusion rates of anti-infective agents through the innerand outer portions 106, 104, respectively of the outer wall 102.

[0024] A further embodiment of the present invention is depicted in FIG.4. Here, a catheter 150 includes an outer wall 152 that envelops a lumen160. As described above, a therapeutic compound may be supplied to thelumen 160 in liquid form, as a rod 158 impregnated with a releasableagent, or in any other suitable form. The outer wall 152 in thisexemplary embodiment is formed of two different materials, havingdifferent diffusion properties. For example, the diffusion properties ofan ethylene vinyl acetate (EVA) catheter may be modified by using anouter shell of polyurethane material outside of the EVA shell.

[0025] As shown in FIG. 4, the outer wall 152 is a composite wall withan inner portion 156 formed, for example, of EVA. An outer portion 154of the wall 152 made, for example, of polyurethane surrounds the innerportion 156. With this arrangement, the diffusion rate of iodine intothe inner portion 156 of the wall 152 is greater than the diffusion ratethrough the outer portion 154 to the outer surface 162. Thus an amountof iodine reaching the outer surface 162 is limited as desired, and thecharge of anti-infective agent present in the lumen 160 will last for alonger period of time. Those skilled in the art will understand that theproperties (materials, thickness, durometers, etc.) of the inner andouter portions 156, 154, respectively, may be adjusted to attain desireddiffusion rates for various agents.

[0026]FIG. 5 shows a schematic diagram of another embodiment of acontrolled diffusion catheter according to the present invention. Inthis exemplary embodiment, a catheter 200 includes an outer wall 220formed of an inner portion 222, which, as described above, have a firstdiffusion rate with respect to anti-infective agents to be supplied tothe catheter 200 contained within lumen 210. A coating 224 is formedaround an outer surface of the inner portion 222. The coating 224 isformed of a material having a diffusion rate of the anti-infectiveagents which is slower than that of the inner portion 222. For example,the inner portion 222 may be formed of polyurethane while the coating224 may be selected from a group of biostable polymers includingpolymers of polyolefins (polyethylene, PVC, PVF, PTFE), polyurethanes(silicones, fluorsilicones, polycarbonate-polyurethane-silicones),cellulosics such as cellulose acetate, polyesters, polyamides (hydroxyamide ethers), polyacrylates, liquid crystal polymers, polystyrene,polycarbonate, polyvinyl alcohols and polyethylene-vinyl alcohol whilethe inner portion 222.

[0027] In a further exemplary embodiment, an impermeable coating may beapplied to the surface of an outer wall of the catheter according to thepresent invention. A secondary process may be used to form pores orchannels of a predetermined size and distribution in the impermeablecoating, to permit a predetermined level of diffusion of theanti-infective agent therethrough. As shown in FIG. 6, a catheter 250includes an outer wall 256 disposed around a lumen 252. As describedabove, a therapeutic compound such as an anti-infective agent may besupplied to a lumen 252. As described above, an inner portion 258 of theouter wall 256 which contacts the contents of the lumen 252, preferablyhas diffusion properties with respect to the contents of the lumen 252which allow a therapeutic agent to be quickly absorbed thereinto. Animpermeable coating 260 is formed around an outer surface of the innerportion 258, forming a cladding around the entire surface of thecatheter 250.

[0028] According to this exemplary embodiment of the invention, theimpermeable coating 260 is processed so that a plurality of pores 264are formed therein, extending from the inner surface 266 to an outersurface 268 of the coating 260. The coating 260 formed of a materialthat is substantially impermeable by the therapeutic agent to besupplied to the lumen 252. Thus, the only way that the agent can reachthe outer surface 268 is via the pores 264. By properly selecting thenumber, size and configuration of the pores 264, a desired diffusionrate through the coating 260 may be obtained. Furthermore, thisdiffusion rate may be varied along the length or around thecircumference of the catheter 250 by altering the distribution or sizeof the pores 264 if an amount of therapeutic agent required at a givenlocation varies. As a result, the therapeutic agent in the lumen 252 isquickly absorbed into the inner surface of the catheter 250 and reachesthe surface 264 at a desired rate to provide a controlled amount ofprotection against infective growth without unduly depleting the supplyof therapeutic agents in the lumen 252.

[0029] As would be understood by those of skill in the art, the pores264 may be formed by any of a mechanical machining process, an etchingprocess, laser drilling or through the use of known photolithographicmethods. It will be understood by those of skill in the art that thecoating 260 may be formed of any material that is impermeable to thetherapeutic agent which is to be supplied to the lumen 252, and that canbe processed to form the desired pores 264. For example, the coating 260may be formed, for example, from an impermeable polymer such as PET.

[0030] The present invention has been described with reference tospecific exemplary embodiments. Those skilled in the art will understandthat changes may be made in details, particularly in matters of shape,size, material and arrangement of parts. For example, although thepresent description referred to an exemplary dialysis cathetercontaining iodine or another anti-infective agent, the invention is notso limited. In addition, although the invention has been described inregard to single lumen catheters, in the case of a dialysis catheter,there would generally be included two lumens—a first for withdrawingblood from the patient and a second for returning treated blood to thepatient. Those skilled in the art will understand that the sameconstruction of a catheter as described above including an outer wallformed of an inner portion having a first rate of agent diffusion and anouter portion with a second rate of agent diffusion may be applied tomulti-lumen catheters including any number of lumens. That is, so longas the inner portion of the catheter wall surrounds the one or morelumens to which the agent is to be supplied, a first rate at which theagent is to be absorbed into the inner portion will be determined by theproperties of the inner portion while the properties of the outerportion of the catheter wall will determine the rate at which agentabsorbed into the inner portion is supplied to an outer surface of thecatheter. Accordingly, by selecting the materials and properties of theinner and outer portions of the catheter wall, the rate of absorption ofagents into the inner catheter wall and the rate of diffusion of theagents to the outer surface of the catheter may be varied to maximizeefficiency in the application of these agents.

[0031] Various other modifications and changes may be made to theembodiments described herein without departing from the broadest scopeof the invention as set forth in the claims that follow. Thespecifications and drawings are, therefore, to be regarded in anillustrative rather than a restrictive sense.

What is claimed is:
 1. A catheter extending from a distal end which,when in an operative position is inserted within a body of a patient, toa proximal end, the catheter comprising: a charge holding cavity towhich a therapeutic compound is to be supplied; and a wall includinginner and outer portions, an inner surface of the inner portionsurrounding the charge holding cavity with an outer portion surroundingat least a portion of an outer surface of the inner portion, wherein theinner portion is formed so that a first diffusion rate of thetherapeutic compound therethrough is different from a second diffusionrate through the outer portion.
 2. The catheter according to claim 1,wherein the second diffusion rate is lower than the first diffusionrate.
 3. The catheter according to claim 1, wherein a durometer of afirst material of which the inner portion is formed is lower than adurometer of a material of which the outer portion is formed.
 4. Thecatheter according to claim 3, wherein the inner and outer portions arecoextruded.
 5. The catheter according to claim 3, wherein the outerportion is less absorptive of the therapeutic compound than the innerportion.
 6. The catheter according to claim 1, wherein the therapeuticcompound is an anti-infective agent.
 7. The catheter according to claim6, wherein the anti-infective agent includes iodine.
 8. The catheteraccording to claim 1, further comprising a rod impregnated with thetherapeutic compound, the rod being insertable into the charge holdingcavity.
 9. The catheter according to claim 1, wherein the charge holdingcavity comprises a lumen of the catheter.
 10. The catheter according toclaim 1, wherein the inner and outer portions are formed of differentmaterials.
 11. The catheter according to claim 10, wherein the innerportion is formed of a polymer and the outer portion is formed of apolymer including one of barium sulfate, titanium oxide and bismuthsub-carbonate.
 12. The catheter according to claim 1, wherein the outerportion contains polyurethane and the inner portion contains EVA. 13.The catheter according to claim 1, wherein the outer portion is formedas a coating surrounding at least a portion of an outer surface of theinner portion.
 14. The catheter according to claim 13, wherein thecoating is formed of one of polymers of polyolefins, polyurethanes,cellulosics, polyesters, polyamides, polyhydroxy amide ethers,polyacrylates, liquid crystal polymers, polystyrene, polycarbonate,polyvinyl alcohols and polyethylene-vinyl alcohol.
 15. The catheteraccording to claim 1, wherein the outer portion is formed as a coatingof a material which is substantially impermeable with respect to thetherapeutic compound, wherein a plurality of pores extend through theouter portion to permit the therapeutic compound to pass therethroughfrom the inner portion to an outer surface of the outer portion.
 16. Thecatheter according to claim 15, wherein the pores are formed by one ofmachining, an etching process and photolithography.
 17. A method ofmaking a catheter, comprising the steps of: forming an inner wallincluding at least one lumen extending therethrough; and forming anouter wall surrounding at least a portion of the inner wall, wherein theouter wall is formed so that a diffusion rate through the outer wall ofa selected agent to be supplied to the lumen is different from adiffusion rate of the agent through the inner wall.
 18. The methodaccording to claim 17, wherein the inner and outer walls are formed sothat the rate of diffusion of the agent through the inner wall isgreater than that through the outer wall.
 19. The method according toclaim 18, wherein the inner and outer walls are coextruded frompolymeric materials.
 20. The method according to claim 19, wherein theouter wall has a greater durometer hardness than the inner wall.
 21. Themethod according to claim 17, wherein the inner wall is formed of an EVApolymer and the outer wall if formed of a polyurethane polymer.
 22. Themethod according to claim 17, wherein the outer wall is formed as apolymeric coating on an outer surface of the inner portion.
 23. Thesystem according to claim 22, wherein the polymeric coating is formed ofa material which is substantially impermeable to the agent, wherein thestep of forming the outer wall comprises the substep of forming aplurality of pores through the polymeric coating.